Biology subjects

Liu, W.

Publications and source records attributed to Liu, W..

32 records · Page 2Linked to original sources

bioRxiv2018

The probiotic effectiveness in experimental colitis is correlated with gut microbiome and host genetic features

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, as a proof-of-concept, we utilized Bifidobacterium longum JDM 301, a widely used commercial probiotic strain in China, to study potential factors that may influence the beneficial effect of probiotics in experimental colitis. We found that the probiotic therapeutic effect was varied across individual mouse even with the same genetic background and consuming the same type of food. The different probiotic efficacy was highly correlated with different microbiome features in each mouse. Consumption of a diet rich in fat can change the host sensitivity to mucosal injury-induced colitis but did not change the host responsiveness to probiotic therapy. Finally, the host genetic factor TLR2 was required for a therapeutic effect of B. longum JDM 301. Together, our results suggest that personalized microbiome and genetic features may modify the probiotic therapeutic effect.

microbiology↗

bioRxiv2018

Oscillatory cortical forces promote three dimensional cell intercalations that shape the mandibular arch

Multiple vertebrate embryonic structures such as organ primordia are composed of a volume of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show 3D mesenchymal cell intercalations, rather than cell divisions and biophysical tissue properties, are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor, we show that cortical force oscillations promote these intercalations. Genetic loss and gain of function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity with cytoskeletal oscillation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin bias and cytosolic calcium transients, respectively, to ensure appropriate tissue form during growth. Our data support oriented 3D cell neighbour exchange as a conserved mechanism driving volumetric morphogenesis.

developmental biology↗

bioRxiv2018

Cullin1 represses systematic inflammasome activation by binding and catalyzing NLRP3 ubiquitination

Activation of the NLRP3 inflammasome is a key process of host immune response, the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages the hosts, and thus it must be precisely controlled. The mechanism underlying the repression of systematic inflammasome activation remains largely unknown. This study reveals that CUL1, a key component of the SCF E3 ligase, plays a critical role in regulation of the inflammasome. CUL1 suppresses the inflammasome activation in HEK293T cells, inhibits endogenous NLRP3 in macrophages, and represses inflammatory responses in C57BL/6 mice. Under normal physiological conditions, CUL1 interacts with NLRP3 to disrupt the inflammasome assembly, and catalyzes NLRP3 ubiquitination to repress the inflammasome activation. In response to inflammatory stimuli, CUL1 disassociates from NLRP3 to release the repression of NLRP3 inflammasome activation. This work reveals a distinct mechanism underlying the repression of inflammasome activation under physiological conditions and the induction of inflammasome activation in response to inflammatory stimuli, and thus provides insights into the prevention and treatment of infectious and inflammatory diseases.

immunology↗

bioRxiv2018

Specific Eph Receptor-Cytoplasmic Effector Signaling Mediated by SAM-SAM Domain Interactions

The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain numerous Eph SAM mutations identified in patients suffering from cancers and other diseases.

biophysics↗

bioRxiv2018

NormExpression: an R package to normalize gene expression data using evaluated methods

Data normalization is a crucial step in the gene expression analysis as it ensures the validity of its downstream analyses. Although many metrics have been designed to evaluate the current normalization methods, the different metrics yield inconsistent results. In this study, we designed a new metric named Area Under normalized CV threshold Curve (AUCVC) and applied it with another metric mSCC to evaluate 14 commonly used normalization methods, achieving consistency in our evaluation results using both bulk RNA-seq and scRNA-seq data from the same library construction protocol. This consistency has validated the underlying theory that a sucessiful normalization method simultaneously maximizes the number of uniform genes and minimizes the correlation between the expression profiles of gene pairs. This consistency can also be used to analyze the quality of gene expression data. The gene expression data, normalization methods and evaluation metrics used in this study have been included in an R package named NormExpression. NormExpression provides a framework and a fast and simple way for researchers to evaluate methods (particularly some data-driven methods or their own methods) and then select a best one for data normalization in the gene expression analysis.

bioinformatics↗

bioRxiv2018

Type-2 CD8+ T lymphocytes responsive to PGD2 and LTE4 in severe eosinophilic asthma

The functions and in vivo roles of type-2 CD8+ T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

immunology↗

bioRxiv2017

Structural and functional MRI from a cross-sectional Southwest University Adult lifespan Dataset (SALD)

Recently, the field of developmental neuroscience has aimed to uncover the developmental trajectory of the human brain and understand the changes that occur as a function of aging. Here we present an adult lifespan dataset of functional magnetic resonance imaging (fMRI) data including structural MRI and resting-state functional MRI. 494 healthy adults (age range: 19-80 years; Males=187) were recruited and completed two multi-modal MRI scan sessions in the Brain Imaging Central of Southwest University, Chongqing, China. The goals of the dataset are to give researchers the opportunity to map the developmental trajectory of structural and functional changes of human brain and to replicate previous findings.

neuroscience↗

bioRxiv2017

Pathway-Level Integration of Proteogenomic data in Breast Cancer Using Independent Component Analysis

Recent advances in the multi-omics characterization necessitate pathway-level abstraction and knowledge integration across different data types. In this study, we apply independent component analysis (ICA) to human breast cancer proteogenomics data to retrieve mechanistic information. We show that as an unsupervised feature extraction method, ICA was able to construct signatures with known biological relevance on both transcriptome and proteome levels. Moreover, proteome and transcriptome signatures can be associated by their respective correlation with patient clinical features, providing an integrated description of phenotype-related biological processes. Our results demonstrate that the application of ICA to proteogenomics data could lead to pathway-level knowledge discovery. Potential extension of this approach to other data and cancer types may contribute to pan-cancer integration of multi-omics information.

cancer biology↗

bioRxiv2017

Parallel loss of symbiosis genes in relatives of nitrogen-fixing non-legume Parasponia

Rhizobium nitrogen-fixing nodules are a well-known trait of legumes, but nodules also occur in other plant lineages either with rhizobium or the actinomycete Frankia as microsymbiont. The widely accepted hypothesis is that nodulation evolved independently multiple times, with only a few losses. However, insight in the evolutionary trajectory of nodulation is lacking. We conducted comparative studies using Parasponia (Cannabaceae), the only non-legume able to establish nitrogen fixing nodules with rhizobium. This revealed that Parasponia and legumes utilize a large set of orthologous symbiosis genes. Comparing genomes of Parasponia and its non-nodulating relative Trema did not reveal specific gene duplications that could explain a recent gain of nodulation in Parasponia. Rather, Trema and other non-nodulating species in the Order Rosales show evidence of pseudogenization or loss of key symbiosis genes. This demonstrates that these species have lost the potential to nodulate. This finding challenges a long-standing hypothesis on evolution of nitrogen-fixing symbioses, and has profound implications for translational approaches aimed at engineering nitrogen-fixing nodules in crop plants.

plant biology↗

bioRxiv2017

Resequencing the Escherichia coli genome by GenoCare single molecule sequencing platform

Next generation sequencing (NGS) has revolutionized life sciences research. Recently, a new class of third-generation sequencing platforms has arrived to meet increasing demands in the clinic, capable of directly measuring DNA and RNA sequences at the single-molecule level without amplification. Here, we use the new GenoCare single molecule sequencing platform from Direct Genomics to resequence the E. coli genome and show comparable performance to the Illumina MiSeq system. Our platform detects single-molecule fluorescence by total internal reflection microscopy, with sequencing-by-synthesis chemistry. With a consensus sequence of 99.71% nucleotide identity to that of the Illumina MiSeq systems, GenoCare was determined to be a reliable platform for single-molecule sequencing, with strong potential for clinical applications.

genomics↗

bioRxiv2017

Combining Semantic Similarity and GO Enrichment for Computation of Functional Similarity

Functional similarity between genes is widely used in many bioinformatics applications including detecting molecular pathways, finding co-expressed genes, predicting protein-protein interactions, and prioritization of candidate genes. Methods evaluating functional similarity of genes are mostly based on semantic similarity of gene ontology (GO) terms. Though there are hundreds of functional similarity measures available in the literature, none of them considers the enrichment of the GO terms by the querying gene pair. We propose a novel method to incorporate GO enrichment into the existing functional similarity measures. Our experiments show that the inclusion of gene enrichment significantly improves the performance of 44 widely used functional similarity measures, especially in the prediction of sequence homologies, gene expression correlations, and protein-protein interactions.\n\nSoftware availabilityThe software (python code) and all the benchmark datasets evaluation (R script) are available at https://gitlab.com/liuwt/EnrichFunSim.

bioinformatics↗

bioRxiv2017

Sugar metabolism changes in response to the ultraviolet B irradiation of peach (Prunus persica L.)

The protected cultivation of peach (Prunuspersica L.) trees is more economical and efficient than traditional cultivation, resulting in increased farmers incomes, but the peach sugar contents are lower than in open planting. In the greenhouse, a high-sugar variety of peach Lumi 1 was irradiated with 1.44 KJ{middle dot}m-2.d-1 intensity ultraviolet B radiation. The soluble sugar contents in fruit, peel and leaf were quantified using liquid chromatography. Overall, sucrose and sorbitol increased before the second fruit-expansion period. To further understand the mechanisms regulating sucrose and sorbitol accumulation in peach fruit, expression profiles of genes involved in sugar metabolism and transport were measured. The activity and translocation protein contents of these enzymes were measured by enzyme-linked immunosorbent assay. The increased sucrose synthase activity and sucrose transporter level in the pericarp promoted the synthesis of sucrose and intake of sucrose into fruit. Sorbitol transport into fruit was promoted by the increased sorbitol transporter protein levels in leaves. In summary, greenhouse the sucrose and sorbitol contents were increased when supplemented with 1.44 kJ{middle dot}m-2{middle dot}d-1 ultraviolet B radiation before the second fruit-expansion period of peach.

plant biology↗

bioRxiv2017

Human brain-derived Aβ oligomers bind to synapses and disrupt synaptic activity in a manner that requires APP

Compelling genetic evidence links the amyloid precursor protein (APP) to Alzheimers disease (AD), and several theories have been advanced to explain the involvement of APP in AD. A leading hypothesis proposes that a small amphipathic fragment of APP, the amyloid {beta}-protein (A{beta}), self-associates to form soluble aggregates which impair synaptic and network activity. Here, we report on the plasticity-disrupting effects of A{beta} isolated from AD brain and the requirement of APP for these effects. We show that A{beta}-containing AD brain extracts block hippocampal long-term potentiation (LTP), augment glutamate release probability and disrupt the excitation/inhibition balance. Notably, these effects are associated with A{beta} localizing to synapses, and genetic ablation of APP prevents both A{beta} binding and A{beta}-mediated synaptic dysfunctions. These findings indicate a role for APP in AD pathogenesis beyond the generation of A{beta} and suggest modulation of APP expression as a therapy for AD.\n\nAcknowledgmentsWe thank Dr. Tiernan T. OMalley for useful discussions and technical advice. This work was supported by grants to DMW from the National Institutes of Health (AG046275), Bright Focus, and the United States-Israel Binational Science Foundation (2013244, DMW and IS); grants to TSJ from Alzheimers Research UK and the Scottish Government (ARUK-SPG2013-1), Wellcome Trust-University of Edinburgh Institutional Strategic Support funds, and the H2020 European Research Council (ALZSYN); and to the Massachusetts Alzheimers Disease Research Center (AG05134).

neuroscience↗

bioRxiv2017

The depletion of MARVELD1 leads to placenta accreta via integrin β4-dependent trophoblast cell invasion

AstractThe mammalian placenta is a remarkable organ. It serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells into the maternal decidua is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin {beta}4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (P<0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin {beta}4 upon the downregulation of MARVELD1 and enhanced migration and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin {beta}4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin {beta}4.

developmental biology↗